Existing algorithms to screen for anal cancer in women living with HIV could be missing many cases of anal high-grade squamous intraepithelial lesions (HSIL) -- abnormal tissue changes that may be a precursor to invasive anal cancer -- according to a study reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

In December the U.S. Food and Drug Administration (FDA) approved a new "9-valent" human papillomavirus (HPV) vaccine from Merck that protects against more cancer-causing strains. The new Gardasil 9 vaccine is expected to prevent about 90% of cervical, anal, and genital cancers. The vaccine is approved for young women ages 9-26 and young men ages 9-15.

Women living with HIV had a higher risk of anal pre-cancerous changes than cervical changes linked to human papillomavirus (HPV), French researchers reported at the 14th European AIDS Conference this week in Brussels. They suggested that all women with HIV ought to be screened routinely for pre-cancerous changes in the anal canal.

The World Health Organization (WHO) last week released new guidance for preventing and controlling cervical cancer, which causes more than 270,000 deaths annually worldwide. The guidelines call for girls to receive 2 rather than 3 doses of the human papillomavirus (HPV) vaccine and for women to be screened using less frequent HPV tests rather than Pap smears.

HIV positive girls did not respond as well to the quadrivalent human papillomavirus (HPV) vaccine as HIV negative girls of the same age, but they responded as well as HIV negative older women, probably giving them sufficient protection from infection, according to a late-breaker presentation at the recent IDWeek conference in San Francisco.

The U.S. Food and Drug Administration this week approved a new "9-valent" human papillomavirus (HPV) vaccine from Merck that protects against infection with more high-risk or cancer-causing strains. The new Gardasil 9 vaccine is expected to prevent about 90% of cervical, anal, and genital cancers. The vaccine is approved for young women ages 9-26 and young men ages 9-15.

Low-income adolescents are not as likely to start or finish the 3-shot human papillomavirus (HPV) vaccine series, which reduces the risk of cervical cancer. Cultural differences can help explain some of the reasons for this disparity and suggest targeted approaches for encouraging vaccination, researchers reported at Second IDWeek conference this week in San Francisco.

Anal infection with high-risk human papillomavirus (HPV) types was common among women with HIV in France, while a Spanish study found a low rate of pre-cancerous anal cell changes in HIV positive women compared with men who have sex with men, researchers reported at the recent 54th Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington, DC.

About two-thirds of gay men and one-fifth of women tested in Spain were found to have abnormalities that could progress to anal cancer, and both groups would benefit from more widespread and accurate testing, researchers reported at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2013) this month in Denver. The men's study found that human papillomavirus (HPV) type 39 was a key risk factor.

HPV can trigger abnormal cell growth ranging from warts to cancer. Certain high-risk or oncogenic types, including HPV-16 and HPV-18, cause anal, cervical, and other genital cancers. These typically begin as low-grade dysplasia (also known as squamous intraepithelial lesions or intraepithelial neoplasia) and can progress to high-grade lesions and then carcinoma if not treated. Lower-risk types including HPV-6 and HPV-11 cause genital warts. However, high-risk types do not always cause dysplasia, low-grade neoplasia does always progress to high-grade lesions or cancer, and lesions may regress on their own without treatment.

Anal cancer is more common among people with HIV than it is in the general population, and prevalence is especially high among men who have sex with men (MSM). Although cervical cancer is considered an AIDS-defining malignancy, anal cancer is not so classified. Regular cervical Pap tests are recommended for both HIV positive and negative women to catch abnormalities at an early stage, but clinical practices for screening, preventing, and treating anal cancer vary widely.

Carmen Hidalgo from Hospital Universitario Virgen de las Nieves in Granada, Spain, and colleagues reported findings from studies looking at HPV infection, anal dysplasia, and predictive factors in men and women with HIV.

Men Who Have Sex With Men

The men's study, presented at an oral session, looked at prevalence of and risk factors for high-grade or stage 2-3 anal intraepithelialneoplasia (AIN) or anal cancer (carcinoma in situ) among HIV positive MSM. The researchers assessed the accuracy of HPV PCR testing for more than a dozen high-risk and low-risk types, cytology (testing for cell abnormalities, as done with a Pap smear), and anoscopy (examination of anal-rectal tissue with a magnifying device). They also compared anoscope-guided cytology vs cytology samples taken with swab.

The analysis included 103 participants in a prospective cohort study that screened HIV positive MSM for anal dysplasia from April 2010 through September 2012 using all 3 methods.

The average age was 36 years and the mean and nadir (lowest-ever) CD4 T-cell counts were 645 and 387 cells/mm3, respectively, indicating well-preserved immune function. Most (85%) used antiretroviral therapy (ART). Half were smokers -- a know risk factors for HPV-related cancer -- and about 40% had anal warts. All the men reported anal sex, they had a median of 1.5 sexual partners during the study, and 70% said they used condoms.

Results

Overall, the researchers found that one-third to one-half of the men had low-grade squamous intraepithelial lesions (LSIL) or stage 1 AIN, and around 5% to 10% had high-grade squamous intraepithelial lesions (HSIL) or stage 2-3 AIN, depending on the method used:

o Anal cytology using swab:

* LSIL: 53%;

* HSIL: 5%;

* Atypical squamous cells of undetermined significance (ASCUS): 5%;

* Normal: 33%.

o Anoscopy (histology):

* AIN 1: 44%;

* AIN 2-3: 10%;

* Carcinoma in situ: 11%;

* Normal: 36%.

o Cytology with anoscope:

* LSIL: 36;

* HSIL: 7%;

* ASCUS: 6%;

* Normal: 50%.

In a univariate analysis looking at separate risk factors, older age and infection with HPV types 6, 39, or 42 predicted high-grade AIN or anal cancer.

In a multivariate analysis, however, HPV-36 was the only independent risk factor to reach statistical significance, conferring more than a 10-fold higher risk (odds ratio 10.51).

Neither smoking nor CD4 count were associated with greater risk in this study, in which CD4 cells were uniformly high.

For each testing method, the researchers calculated sensitivity (ability to detect true cases), specificity (ability to rule out if not present), positive predictive value (PPV, or proportion of correct positive diagnoses), and negative predictive value (NPV, or proportion of correct negative diagnoses):

If cytology is abnormal, irrespective of the grade of dysplasia, histological evaluation of the lesion should be performed using anoscopy, they added. But if cytology is normal, HPV PCR screening should be done, and if high-risk HPV is found, the patient should also be referred for anoscopy.

Asked if anal screening could be done less often after a series of negative tests -- as is the case for HIV negative women undergoing cervical screening -- Hidalgo Tenorio said she recommends ongoing screening every year for this population.

Session moderator Judith Aberg asked about the unexpectedly high rate of HPV-39, speculating whether widespread vaccination against HPV types 16 and 18 might allow other types to take over as major causes of cancer. Hidalgo Tenorio did not have an answer, but to date HPV vaccines have mostly been given to young women, and more recently young men, so coverage is likely still low in this population. She noted that new vaccines are under study that will protect against more HPV types than current vaccines.

Women with HIV

Hidalgo Tenorio's team also presented a poster looking at the prevalence of and risk factors for anal dysplasia among a cohort of women in southern Spain, comparing rates to those of men who have sex with men.

While cervical abnormalities are a known risk for women with HIV, anal dysplasia may be equally or more common, though it is not regularly screened for. The researchers noted that HIV positive women have a 14-fold higher risk of anal neoplasia than HIV negative women.

This cross-sectional analysis looked at HIV positive women and MSM receiving medical care at a single center in southern Spain between December 2008 and December 2012. The men were the same group described above.

The 45 women were a bit older, with an average age of 43 years. Mean and nadir CD4 T-cell counts were 692 and 223 cells/mm3, respectively, and most (93%) were taking ART. A majority (71%) were smokers, 22% had anal warts, and 27% were coinfected with hepatitis C (compared with only 4% of the men). They reported a median of 1 sexual partner during the study, 53% said they used condoms, and only 22% reported anal sex.

Results

23% of the women had low-risk HPV types and 34% had high-risk types, compared with 71% and 85%, respectively, among the men.

Looking at high-risk types among women, 5% had HPV-16, 5% had HPV-18, 9% had HPV-51, and 2% had HPV-53; for men, the corresponding prevalence rates were 27%, 17%, 18%, and 15%, respectively.

More than three-quarters of the women (79%) had normal cytology by anal swabs, compared with one-third of the men.

8 women (19%) had LSIL, none had HSIL, and 1 (2%) had ASCUS.

In a univariate analysis, significant risk factors for anal dysplasia were presence of either low-risk of high-risk HPV types, with HIV viral load and CD4 count being of borderline significance.

In a multivariate analysis, however, presence of anal or genital warts was the only independent risk factor (OR 11.5)

Rates of dysplasia and anal HPV infection in this cohort of HIV positive women were significantly lower than those of HIV positive MSM, but even they are high enough to justify screening regardless of virological or immunological status, the researchers concluded.

They did not answer the question put forth in their title -- whether anal dysplasia among people with HIV is a matter of sexual behavior or gender -- but HPV is sexually transmitted, and the women in this study were much less likely than the gay men to have had anal sex.

The quadrivalent human papillomavirus (HPV) vaccine worked as well for teens and young adults with HIV as it did for their HIV negative counterparts, according to study findings presented the 20thInternational AIDS Conference last week in Melbourne.

Vaccination against human papillomavirus (HPV) types 16 and 18 reduced oral infection by more than 90% in a large study in Costa Rica, which is likely to bring down the rate of mouth and throat cancers in years to come, according to a report in the July 17, 2013, online edition of PLoS ONE.

HIV positive women respond well to the Gardasil human papillomavirus (HPV) vaccine, offering them protection against cervical cancer, according to a study published in the April 14 electronic edition of Clinical Infectious Diseases. Related recent research found that both Gardasil and Cervarix are effective in people with HIV.

A large number of infections with anal cancer-associated strains of human papillomavirus (HPV) among older gay men could be prevented with the use of HPV vaccines, Australian research reported at the recent 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur. A related analysis showed that high-grade pre-cancerous cell changes were common but often resolved spontaneously.

The progression of anal dysplasia is highly variable in people with HIV, progressing in some and remaining stable or regressing in others, according to a retrospective analysis of nearly 3000 participants presented at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) last week in Boston. Progression to invasive anal cancer, however, was uncommon.

Actor Michael Douglas' claim that his throat cancer was caused by oral sex has brought new attention to the link between human papillomavirus (HPV) and oral cancer, as well as heightened interest in HPV vaccination for both girls and boys. Recent studies suggest that spouses of people with oral cancer are not themselves at higher risk, 2 vaccine doses may work as well as 1, and vaccination has already reduced genital warts in Australia.

African-American women with precancerous cervical abnormalities are about half as likely to have cancer-causing human papillomavirus (HPV) types 16 and 18, and more likely to have other types for which the Gardasil and Cervarix vaccines do not provide protection, according to a study presented at the American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research taking pace this week in Maryland.

A small proportion of lung cancers may be caused by the same high-risk strains of human papillomavirus (HPV) associated with cervical and anal cancer, according to recently reported study findings, which could help explain an apparent link between higher lung cancer rates and immune deficiency in people with HIV.

Only 20% of people with HIV in Europe have fully suppressed viral load, compared to an estimated 24% in sub-Saharan Africa, despite much higher rates of HIV diagnosis in the European region, Professor Jens Lundgren of the University of Copenhagen told the 14th European AIDS Conference in Brussels on Saturday.

Performing random anal biopsies increases the rate of diagnosis of high-grade squamous intraepithelial lesions (HSIL) during high-resolution anoscopy, researchers from Mt. Sinai School of Medicine in New York City reported at the recent 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013).